Defining ''full-length'' recombinant factor VIII: a comparative structural analysis

Coagulation factor VIII (FVIII) is an important glycoprotein co-factor involved in haemostasis, functioning to accelerate activation of factor X by activated factor IX. Insertion of expression vectors containing the full-length cDNA sequence of human FVIII into mammalian cell lines results in the production of recombinant factor VIII (rFVIII), typically referred to as 'full-length' rFVIII (FLrFVIII). Both FLrFVIII and plasma-derived FVIII exist primarily as heterodimeric proteins, consisting of a heterogenous light and heavy chain. The objectives of this study were to compare the structural heterogeneity of high-purity FVIII preparations and further define the term 'full length' as it refers to rFVIII protein structure. Five commercially available FVIII concentrates were characterized based on SDS-PAGE, N-terminal sequencing, and peptide and domain mapping coupled to mass spectrometry. The major heavy chain species identified in FLrFVIII included various B-domain-truncated forms of FVIII, with the predominant species terminating at Arg(1313). This study demonstrates that the use of full-sequence FVIII cDNA for the production of rFVIII does not result in a homogeneous FLrFVIII protein product. Rather, commercially available FLrFVIII represents a heterogenous mixture of various B-domain-truncated forms of the molecule, with no evidence of a contiguous, intact B-domain.     

EDI results of Japanese and German women and possible sociocultural explanations

The goal of this study was to compare data for women with bulimia nervosa and for a healthy control group both in Japan and Germany. These data were obtained using the Eating Disorder Inventory (EDI‐2). In Germany, EDI‐2 data and BMI values were collected from 102 nurses in training, 57 female medical students, and 29 patients with bulimia nervosa. In Japan, data were gathered from 243 female ‘short college’ students and 20 patients with bulimia nervosa. The Japanese non‐clinical control group showed significantly higher values on nearly all EDI scales than the German control group. They had a markedly higher drive for thinness, though their BMI values were lower. When the German and the Japanese bulimia nervosa patients were compared, the Japanese patients also showed higher values than their German counterparts on three EDI scales, but these differences were negligible. It is suggested that sociocultural factors in Japan, in particular a significant dependency on social norms, may contribute to the high EDI values. Copyright © 2005 John Wiley & Sons, Ltd and Eating Disorders Association.     

In vitro fertilisation in domestic mammals—a brief overview

Many factors influence the final oocyte maturation, fertilisation, and early embryo development, and there are both similarities and differences between species. When comparing the advancement of assisted reproductive technologies (ARTs), the development in the bovine species is not far behind the medical front, with around one million in vitro-produced bovine embryos each year. This rate of progress is not seen in the other domestic species. This review aims to give an overview of the development and specific difficulties of in vitro embryo production in various domestic animal species, with the main focus on cows, pigs, and cats. In production animals, the aim of ARTs is commonly to increase the genetic progress, not to treat reproductive failure. The ARTs are also used for preservation of genetic diversity for the future. However, specifically for oocyte maturation, fertilisation, and early embryonic development, domestic mammals such as the cow and pig can be used as models for humans. This is particularly attractive from an animal welfare point of view since bovine and porcine oocytes are available in large numbers from discarded slaughterhouse material, thereby decreasing the need for research animals. Both for researchers on the animal and human medical fronts, we aim for the development of in vitro production systems that will produce embryos and offspring that are no different from those conceived and developed in vivo. Species-comparative research and development can provide us with crucial knowledge to achieve this aim and hopefully help us avoid unnecessary problems in the future.     

湖南省郴州市一起新型冠状病毒肺炎聚集性疫情流行病学调查

目的 通过分析郴州市一起新冠肺炎聚集性疫情相关病例发病确诊过程,探讨新冠病例早发现、早报告以及病例诊断和隔离观察解除的策略依据。 方法 对该起新冠肺炎聚集性疫情的病例和密切接触者进行现场流行病学调查,描述性分析流行病学史、临床和实验室资料。 结果 利用大数据比对监测,在转送监测对象至集中场所隔离医学观察时发现了新冠肺炎确诊病例何某华,由此发现一起新冠肺炎家庭聚集性疫情,何某的5名密切接触者中有3人发病确诊（包含1名重症病例）,其中重症病例黄某第7次新型冠状病毒核酸检测阳性进而确诊,密切接触者中胡某有流行病学史、血常规白细胞下降和肺炎影像学改变,但是5次咽拭子核酸检测阴性,未确诊。 结论 大数据比对监测对发现传染病有积极作用;早期对有流行病学史人员单独隔离医学观察对防止聚集性疫情发生有重要意义;将2次核酸检测阴性作为新冠肺炎病例的排除标准和将核酸检测阳性作为确诊新冠肺炎病例的必备条件,值得探讨,这都可能放走传染源,导致新冠肺炎传播。     

Evaluation and comparison of in-vitro dissolution profiles for different brands of amoxicillin capsules

Background

Amoxicillin is an oral semi-synthetic, β-lactam antibiotic used to treat bacterial infections caused by susceptible micro organisms. It is usually prepared in capsule, tablet and powder for oral suspension form. Solid dosage forms for oral administration pose bioavailability problems related to the absorption process The World Health Organization (WHO) has promoted the use of generic brands in order to make the cost of medicines affordable. Generic substitution could be considered when a generic copy of a reference drug contains identical amounts of the same active ingredient in the same dose formulation and route of administration. However, the presences of generic products those are not interchangeable with that of the innovator and/or with each others have been reported.

Objectives

To evaluate and compare the in-vitro dissolution profiles of different generic brands of amoxicillin capsules with the innovator that are available in Ethiopian market.

Methods

Dissolution profiles for nine brands of amoxicillin capsules contained amoxicillin 500 mg which are available in Ethiopian market were determined using a method from the United States Pharmacopoeia (USP, 2009). The obtained dissolution profile data of the eight brands were evaluated and compared with the innovator brand (Amoxil™) using two different statistical methods: the fit factors (f1 & f2) and the dissolution efficiency (D.E.) model. Most generic brands of amoxicillin capsules (62.5% of the tested brands) are not interchangeable with the innovator brand.

Results

The calculated f1 factor for Brand A and Brand G are 10.1 and 1.1 respectively. However, for the rest six brands the f1 factors are greater than 15. The f2 factor for Brand G is 74.1 and for Brand A is 48.5 which is near to 50. Similarly, the f2 factors for the six brands are less than 50 which support the result of the f1 factors for the dissimilarity of these brands with the innovator brand. The mean dissolution efficiencies as well as the 95% confidence intervals are within ±10% only for two brands, Brand F and Brand G.

Conclusions

Most generic brands of amoxicillin capsules (62.5%) are not interchangeable with the innovator brand (Amoxil™).